Drug addiction is typically characterized by a physical, as well as psychological dependence. To treat drug dependence, a drug substitute is administered to the addict according to an established treatment schedule. Adherence to the treatment schedule determines the effectiveness of the treatment. Accordingly, such dependencies are treated as part of a drug cessation program which includes both administration of a drug substitute and behavior modification counseling.
Examples of drug dependencies displaying both physical and psychological addiction include dependences on heroin, non-opiate sedatives (including barbiturates), benzodiazepines, cocaine and alcohol. Nicotine dependence is one example of a drugug dependency in which the drug of abuse exerts both a physical and psychological addiction.
Recent studies have linked smoking to both heart disease and cancer. Smoking also may adversely affect a fetus during pregnancy. A trend thus has developed towards people wanting to quit smoking. It is difficult for a person to quit smoking since nicotine, a component of tobacco, is an addictive drug ("Nicotine Addiction", a report of the Surgeon General, 1988). Presently available over-the-counter products for aiding in smoking cessation are not always successful.
Lobeline is an alkaloid obtained from the dried leaves and tops of the Indian tobacco herb, Lobelia inflata. Lobeline is a substituted piperidine compound that produces several physiological affects, some of which are similar to those produced by nicotine. Lobeline's potency in causing these physiological effects is significantly less than that of nicotine. Because of lobeline's pharmacological similarities with nicotine, it has been considered as a substitute for nicotine which assists individuals in lessening addiction to nicotine and in ceasing to smoke cigarettes. Although use of lobeline as a smoking cessation aid has been studied since at least the 1930's, its efficacy has been a matter of dispute. Moreover, severe, undesirable side-effects have been reported.
Presently available over-the-counter products (Nikoban.RTM., Bantron.RTM., CigArrest.TM., and Nic-Fit) offer lobeline hemi-sulfate as an aid to smoking cessation. These products are taken orally and the recommended daily doses are up to 6 milligrams. Antacids are incorporated in some of the products to overcome gastrointestinal discomfort, a side effect similar to that caused by nicotine. Higher oral doses may not be feasible because of the concomitant gastric upset. The efficacy of oral doses of lobeline at 6 mg/per day in aiding smoking cessation has not been proven.
The presently available over-the-counter lobeline formulations for treating smoking addiction either do not appear to provide or do not appear to maintain therapeutic blood or tissue levels of lobeline. This may be because of the low dose of lobeline in the lobeline formulations, poor absorption of oral formulations or metabolism which does not allow lobeline to reach critical therapeutic levels.
Although there have been reports of using lobeline in oral formulations at doses in excess of 10 mg/day, nausea and even vomiting have been associated with such doses. A further problem with such oral dose regimens is that self-administration of as many as 18 tablets per day has been required. This not only may be considered by patients as intrusive, but also does not permit the physician to carefully control dosage..
Kalyuzhnyy (J. of Neural Psychiat 68: 1864-1870 (1968)) describes the use of intramuscular doses of lobeline hemi-sulfate up to 10 mg/per injection, administered twice daily. Although the amount of lobeline administered by Kalyuzhnyy was reported to be effective, the procedure for administration does not lend itself to practical application because it requires twice daily injections of lobeline.
Takagi et al. (JP 1-197,435) describe a smoking-substitute adhesive agent containing 0.5 to 10 percent lobeline by weight. Takagi et al. report that blood concentrations of lobeline remained higher for several hours compared to blood concentrations of nicotine delivered using the same adhesive agent delivery system. Takagi et al. did not report the amounts of lobeline released from the adhesive agent.
The accepted program for treating heroin addiction has been to incorporate a drug substitute, e.g., methadone, into an oral formulation for administration to the drug addict. The effectiveness of such treatment depends largely upon adherence to an established treatment schedule. Accordingly, out-patients are provided with a limited number of doses with specific instructions as to frequency of use. Oral doses are often provided as a powder or tablet which can be readily dissolved in fruit juices for administration. One problem associated with such water soluble compositions is that the composition can alternatively be dissolved in water, filtered and concentrated to provide a solution sufficiently rich in the drug substitute to be abused by the addict, i.e., injected in lieu of the drug of abuse.